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HRA004834
   HRA004834.xlsx
Title:
Novel interferonopathy due to dominant negative REXO2
Release date:
2024-07-19
Description:
Mitochondrial RNA (mtRNA) in the cytosol can trigger the innate immune sensor MDA5, and autoinflammatory disease due type I IFN. Here we describe a new disease in this class of interferonopathy, due to a dominant negative mutation of the mitochondrial exonuclease REXO2. This heterozygous de novo mutation (p.T132A) caused persistent skin rash featuring hyperkeratosis, parakeratosis and acanthosis with infiltration of lymphocytes and eosinophils around small blood vessels. There was also consistent elevation in circulating IgE levels, inflammatory cytokines including IFNa, and a type I IFN gene signature in PBMC. Mechanistically, REXO2 (T132A) lacks the ability to cleave RNA, and inhibits the activity of wild-type REXO2. This leads to an accumulation of mitochondrial dsRNA in the cytosol, which is recognized by MDA5, leading to the associated type I IFN gene signature. Therefore, appropriate regulation of mitochondrial RNA by REXO2 is required to prevent this novel inborn error of immunity.
Data Accessibility:   
Controlled access Request Data
BioProject:
PRJCA017695
Study type:
Cell line related study
Data Access Committee

For each controlled access study, there is a corresponding Data Access Committee(DAC) to determine the access permissions. Access to actual data files is not managed by NGDC.


DAC NO.:
HDAC002728
DAC name:
zhang/Elina_REXO2
Contact person:
Zhang Yuxia
Email:
yuxia.zhang@gwcmc.org
Description:
Profiling of a new disease of the class of interferonopathy, due to a dominant negative mutation of the mitochondrial exonuclease REXO2
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Submitter:   Zhang Yuxia / yuxia.zhang@gwcmc.org
Organization:   Guangzhou Women and Children's Medical Center
Submission date:   2023-06-14
Requests:   -